Abstract
Lipopolysaccharide (LPS) is the main virulence factor of Gram-negative bacteria, which can incite inflammation in tissues by inducing cells to secrete a variety of proinflammatory mediators, including cytokines, chemokines, interleukins, and prostaglandins. Herein, we chose LPS as an inducer to establish an inflammatory model of HeLa cells, and explored the effects of LPS on energy metabolism. We treated HeLa cells with different concentrations (0, 0.4, 1.0, 2.0, 4.0, and 6.0 μg/mL) of LPS for 24 h, and explored its effects on intercellular adenosine triphosphate (ATP) levels, intercellular nitrous oxide (NO) content, mitochondrial functions, and enzyme activities related to energy metabolism. Furthermore, we used metabonomics to study the metabolites that participated in energy metabolism. We found a positive correlation between LPS concentrations and intracellular ATP levels. In addition, LPS increased intracellular NO production, altered mitochondrial functions, strengthened glycolytic enzyme activities, and changed metabolites related to energy metabolism. Hence, in this study, we showed that LPS can strengthen energy metabolism by enhancing glycolysis, which could be used as an early diagnostic biomarker or a novel therapeutic target for inflammation-associated cancers.
Highlights
Cancer is a worldwide public health problem and poses a severe threat to human health and life [1]
We treated HeLa cells with different concentrations (0, 0.4, 1.0, 2.0, 4.0, and 6.0 μg/mL) of LPS for 24 h, and explored its effects on intercellular adenosine triphosphate (ATP) levels, intercellular nitrous oxide (NO) content, mitochondrial functions, and enzyme activities related to energy metabolism
We found that LPS could increase the ATP level in HeLa cells
Summary
Cancer is a worldwide public health problem and poses a severe threat to human health and life [1]. The tumor microenvironment (TME) plays a pivotal role in tumor initiation, progression, and metastasis. It is a complex and heterogeneous assembly characterized by elevated lactate levels, low glucose and nutrient levels, acidic extracellular pH levels, and multiple cytokines and growth factors [2,3]. Cancer cells have a strong demand for adenosine triphosphate (ATP) to sustain the anabolic processes of growth and proliferation. Tumors prefer a hypoxic environment, utilizing glycolysis to produce ATP, even in the presence of sufficient oxygen [4,5], which is called the Toxins 2018, 10, 441; doi:10.3390/toxins10110441 www.mdpi.com/journal/toxins. The Warburg effect can be weakened or strengthened when the tumor microenvironment conditions are changed [6,7,8]
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